This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Hypoglycemia Prevention After Exercise in Adolescent T1DM Patients Using a Control to Range System (NCT01390259), a randomized na study. The primary outcome is Hypoglycemic Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01390259 |
| Phase | NA |
| Condition | Type 1 Diabetes Mellitus |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Virginia |
| Results posted | Yes |
2. Clinical Question
Population
Adolescents with type 1 diabetes mellitus. The registry record lists an enrollment of 11.
Intervention
Closed-loop control, in which a computer made recommendations for insulin treatment using a system based on continuous glucose monitoring.
Comparator
Open-loop management, in which participants were in charge of their insulin treatment.
Primary question
The primary endpoint was hypoglycemic events per patient during a 22-hour timeframe. The record does not report a comparative result for this endpoint.
The study was designed to compare glucose management under the two approaches in adolescents with type 1 diabetes. Its stated focus was avoiding hypoglycemic events while managing glucose during meals and mild exercise. In the protocol summary, the system is described as using continuous glucose monitoring and information about insulin treatment to make recommendations intended to manage glucose excursions.
The primary endpoint counted events below 70 mg/dL per patient. An event was defined as consecutive YSI plasma glucose measurements below that threshold or moderate hypoglycemic symptoms. This measure concerns the frequency of events, rather than the amount of time spent at a particular glucose level or the average glucose value. Percent time in euglycemia and mean glucose were listed as secondary outcomes.
The clinical question is therefore whether hypoglycemic-event frequency differed between the two management approaches in this study population. The registry record does not provide endpoint values, an effect estimate, a confidence interval, or an analysis comparing the treatments. It consequently does not establish the direction or size of any difference. The recorded study design and endpoint define the question; they are not themselves evidence of a treatment effect.
3. Trial Design
The registry record describes a randomized, unmasked, crossover study of open-loop and closed-loop insulin management. In a crossover design, participants receive more than one treatment condition, so comparisons can be made within participants as well as between treatment conditions. The record identifies the two treatment approaches but does not report the sequence assigned to participants, the timing of each treatment period, or whether any washout interval was used.
In the open-loop arm description, participants were in charge of their insulin treatment. In the closed-loop description, a computer made recommendations. The study summary characterizes the closed-loop system as modular insulin management based on continuous glucose monitoring and directed toward avoiding hypoglycemic and prolonged hyperglycemic episodes. The study was unmasked, so the registry does not describe masking of participants or investigators.
The listed enrollment was 11. The protocol summary says investigators planned to enroll 12 adolescents and expected retention of 10/12. Those are planning statements, not a report of the number who completed each treatment condition or contributed endpoint data. Completion by treatment period and analysis population are not reported in the registry record.
The summary describes 24h inpatient admissions with 30 minutes of mild exercise and 3 meals as challenges to the insulin management system. It also describes a study schedule involving screening, continuous glucose monitoring insertions, and inpatient admissions. The summary text ends before fully specifying how insulin coverage varied, so the details of that aspect are not reported in the registry record.
The study status is completed, with a start date of 2010-01 and primary completion date of 2011-02. The registry record does not report the statistical analysis plan, treatment-period procedures, or a numerical comparison of outcomes. These omissions limit how fully the conduct and analysis can be reconstructed from the record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Open-Loop First, Then Closed-Loop | Closed-Loop Control First, Then Open-Loop |
|---|---|---|
| STARTED | 5 | 6 |
| COMPLETED | 5 | 6 |
| NOT COMPLETED | 0 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Adolescents |
|---|---|---|
| Participants analysed | 11 | |
| Age, Continuous | years | 14.5 (SD 1.5) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 6 |
| HbA1c | percent | 8.6 (SD 0.8) |
6. Primary Endpoint
The registry lists the primary outcome as Hypoglycemic Events, measured over 22 hours.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | events/patient |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is titled Hypoglycemic Events and is expressed as events per patient. It is a mean of a continuous measure, with standard error identified as the dispersion measure in the endpoint description. The timeframe is 22 hours. The event definition is consecutive YSI plasma glucose measurements below 70 mg/dL or moderate hypoglycemic symptoms.
This endpoint was selected to describe the frequency of hypoglycemic events during the specified observation period. Event frequency is distinct from the duration or severity of an episode, and it does not directly describe average glucose or the proportion of time spent in a glucose range. The registry lists percent time in euglycemia and mean glucose as secondary outcomes, which address different aspects of glucose patterns.
General: an event-count endpoint can be useful when the question concerns how often a defined event occurs. Its interpretation depends on a consistent event definition and comparable observation time. In this study, the stated threshold and symptom criterion define what qualifies as an event. The record does not explain how overlapping or recurrent measurements were grouped beyond the wording of that definition.
No primary-endpoint mean, standard error, treatment contrast, confidence interval, or test result is reported in the registry record. The endpoint description therefore identifies what the investigators intended to measure, but it does not establish how frequently events occurred under either treatment or whether the conditions differed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question, design, and endpoint definition, but it does not contain a reported comparison of hypoglycemic events between closed-loop and open-loop management. The number of analyses is listed as 0, and the primary outcome is not reduced to one comparison because it has several categories or time points. No treatment-specific means, standard errors, effect estimate, confidence interval, or p-value are reported. There is therefore no numerical result from which to describe the observed direction, magnitude, or precision of a treatment difference.
This distinction matters: a completed study is not the same as a reported analysis. The record's status indicates completion, while the listed outcomes and endpoint definitions describe what was measured or intended to be measured. Neither the design nor the stated goal of preventing hypoglycemia shows whether the observed data favored either treatment.
The registry lists two secondary outcomes: percent time in euglycemia and mean glucose. Their names indicate additional aspects of glucose control, but outcome values and comparative analyses are not reported in the registry record. It is not possible to determine whether the secondary outcomes were measured completely, how they were summarized, or whether their results agreed with the primary endpoint.
General: an effect estimate describes the observed contrast between treatments, while a confidence interval expresses the uncertainty around that estimate under the statistical model used. A p-value, when reported, addresses compatibility of the data with a specified null hypothesis; it does not by itself measure clinical importance or the probability that a treatment is effective. None of these quantities is available for the primary comparison in the registry record.
Because the study is crossover, within-participant comparisons may be relevant to interpretation. General: such designs can account for stable differences between participants, but interpretation also depends on treatment sequence, period effects, and whether effects carry over from one period to another. The registry record does not report how these considerations were addressed. Without the observed data and analysis details, no inference about a treatment difference can be drawn from the design label alone.
The record's sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is not the trial's own design justification, and no specific numerical planning results or observed effect are reported in the registry record. Such an illustration should not be read as observed power or as evidence that a result was precise.
The defensible interpretation is limited: the registry records a randomized crossover comparison in adolescents with type 1 diabetes, identifies hypoglycemic events as the primary endpoint, and lists no analyses. It does not report whether event frequency differed, how large any difference was, or how uncertain an estimate would be.
9. Statistical Methods Explained
General: statistical methods connect a study question to a defined outcome and a comparison. The design determines what observations are available, while the analysis plan specifies how those observations are used. For this trial, the registry identifies randomization, no masking, a crossover model, a primary endpoint, and two secondary outcomes. It does not report the statistical analysis plan or any endpoint analysis results.
What does randomization contribute?
General: randomization assigns treatment conditions by chance rather than by participant or investigator choice. It is intended to reduce systematic differences in treatment assignment. In a crossover study, randomization may apply to treatment sequence; however, the registry record does not state the sequence procedure. Randomization does not, by itself, ensure that all data are complete, eliminate measurement error, or guarantee that an estimate is precise.
How does a crossover comparison work?
General: in a crossover design, each participant receives multiple treatment conditions, and the outcome under one condition can be compared with the outcome under another for that same participant. This can account for stable participant characteristics that would otherwise contribute to variation between people. The analysis must also consider the order of treatment periods and changes over time. If a treatment's effect persists into a later period, a carryover effect can complicate the comparison. The registry record does not report treatment sequence, period structure, washout procedures, or how period and carryover effects were handled.
The study is described as unmasked. General: lack of masking can affect how participants or study staff behave, how symptoms are reported, or how outcomes are assessed, especially when an endpoint includes symptoms as well as measurements. The registry record does not explain whether the symptom component was assessed by a masked assessor or whether any other safeguards were used.
What does the primary summary measure mean?
The endpoint is a mean number of events per patient, with standard error identified as the dispersion measure. General: a mean summarizes the average outcome in a group or condition. A standard error describes the uncertainty in an estimated mean, rather than the spread of individual observations. The standard deviation, by contrast, describes variability among observations. These quantities answer different questions and should not be treated as interchangeable. The registry record reports no endpoint mean or standard error for either treatment.
General: event counts can have a distribution different from a normally distributed measurement. Counts may be unevenly distributed, and a small number of participants with many events can influence a mean. Over-dispersion refers to variability greater than expected under a simple count model; if present, ignoring it can make uncertainty estimates unreliable. Appropriate modeling depends on the observed distribution, observation time, and analysis objective. The registry record does not report a count model, a dispersion assessment, or an adjustment for observation time beyond the stated 22-hour timeframe.
How should uncertainty be assessed?
General: a confidence interval gives a range of values compatible with the data and the chosen statistical procedure. A narrow interval indicates greater precision than a wide interval, but interpretation also depends on whether the interval includes values that would matter scientifically or clinically. A p-value is tied to a specified null hypothesis and model assumptions. It is not an estimate of the size of an effect. The record reports no confidence interval or p-value for the primary endpoint, so neither precision nor statistical compatibility can be assessed from it.
The crossover structure makes the unit of comparison important. General: an analysis that treats repeated observations from the same participant as independent can misrepresent uncertainty because outcomes from one person may be related. A paired or otherwise participant-aware method can account for this dependence, depending on the data and design. The registry record does not state which method was used, and it does not provide participant-level or treatment-period summaries.
What does the planning illustration describe?
The stated assumptions for the sample-size planning illustration are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustration is described as computed from the observed effect, with the effect to detect expressed as a fraction of that observed effect. These assumptions describe a planning calculation, not the trial's own design justification. The registry record does not report a sample-size justification, and it does not give numerical illustration results or the observed effect needed to interpret them.
General: sample-size calculations estimate how many participants may be needed under specified assumptions to detect a target effect with a chosen probability, often called power. Their outputs depend on assumptions about variability, effect size, allocation, and analysis. A planning calculation is not observed power: it cannot establish how informative the completed study's data were. A completed study's precision is better judged from its estimate and uncertainty interval, neither of which is reported.
In this crossover study, the stated equal-allocation assumption in the planning illustration should not be taken as a description of how participants were assigned to treatment sequences. The registry record describes the trial as crossover but does not give the sequence allocation details. The illustration's assumptions and the actual design are therefore distinct pieces of information.
Overall, the available methods information identifies the design and endpoint but leaves the analysis choices undocumented. The registry record does not report how repeated observations were modeled, how missing outcomes were treated, how the secondary outcomes were analyzed, or how multiple comparisons were handled. Those omissions prevent a detailed appraisal of the statistical analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists Hypoglycemic Events as the primary outcome and lists Percent Time in Euglycemia and Mean Glucose as secondary outcomes. It also records three outcome measures and indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The number of analyses is listed as 0. The registry record does not report a multiplicity strategy, such as a prespecified hierarchy, adjustment across outcomes, or a rule for interpreting multiple comparisons.
General: examining several outcomes, time points, or categories creates multiple opportunities to observe apparently notable results by chance. A multiplicity approach specifies how those comparisons will be interpreted or adjusted. Without a reported plan and actual results, it is not possible to determine what comparisons were conducted or how any findings should be considered alongside one another.
Missing-data methods and analysis populations are not reported in the registry record. The protocol summary expected retention of 10/12 while the recorded enrollment is 11, but it does not give treatment-period completion, endpoint availability, reasons for missing observations, or the number included in any analysis. The expectation is a planning statement and should not be treated as an observed completion figure.
General: missingness can affect a treatment comparison when the availability of outcome data is related to participants' health, treatment, or measured outcomes. An analysis population definition clarifies which randomized participants or observations contribute to an estimate. The approach to missing data can influence both the estimate and its uncertainty. Because the record reports neither missing-data methods nor analysis populations, their influence cannot be assessed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Adolescents | 0 | 11 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Adolescents | 0 of 11 |
The registry's adverse-event listing has a group titled Adolescents. It records 11 at risk, 0 affected for serious events, and 0 affected for other events. These are the figures in the registry record; they are not a comparison of safety between the closed-loop and open-loop conditions. The record does not provide treatment-specific adverse-event figures or identify event terms.
The deaths field is not populated with a count. Deaths are therefore not reported in the registry record, rather than reported as 0. The list of top serious-event terms is empty, and the record does not provide descriptions, timing, severity beyond the serious-event category, or attribution of events to treatment.
General: an at-risk count describes the population included in the reporting group, while an affected count describes recorded events or people affected according to the registry's reporting convention. Those figures should be interpreted within the reporting scope and should not be assumed to capture every possible adverse effect. A small study and an absence of recorded events do not establish that an intervention is free of risk. The record's adverse-event figures provide limited descriptive information and do not support a comparative safety conclusion.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized, unmasked crossover study comparing computer-recommended closed-loop insulin management with open-loop management in adolescents with type 1 diabetes. It identifies a primary endpoint of hypoglycemic events per patient over 22 hours, defined using consecutive YSI plasma glucose measurements below 70 mg/dL or moderate hypoglycemic symptoms. These details establish the intended clinical and statistical question.
They do not establish the answer. No primary outcome values or comparative analysis are reported, and the record lists 0 analyses. There is no reported treatment contrast, confidence interval, or p-value. It is not possible to say from this record whether one management approach was associated with fewer events, whether any observed difference was large or small, or how precise an estimate would be.
The record also names percent time in euglycemia and mean glucose as secondary outcomes, but does not report their values or analyses. The safety listing reports 0 affected for serious events and 0 affected for other events in the Adolescents group, with 11 at risk; deaths are not reported. These entries are limited registry summaries and do not constitute a detailed or treatment-specific safety comparison.
General: a study's design can make a comparison possible, but interpretation requires the observed data, an appropriate analysis, and information about uncertainty. A sample-size planning illustration cannot substitute for those results, and it should not be described as observed power. Similarly, a study's stated aim is not evidence that its intervention achieved that aim.
The appropriate conclusion is narrow: the registry record documents a completed crossover study and its planned glucose-related outcomes, but does not report results that answer the primary comparison. No conclusion about the direction, size, precision, or clinical importance of a treatment difference can be drawn from the available record.
13. Why This Trial Matters Statistically
This study raises a useful statistical question because it combines a crossover design with an event-frequency endpoint. Crossover studies can support within-participant comparisons, while event counts describe how often a defined outcome occurs. Both features make the analysis choices important: repeated observations from a participant are related, and event-count data may be unevenly distributed.
The endpoint definition also illustrates why measurement details matter. Hypoglycemic events were defined using both glucose measurements and moderate symptoms. The measurement threshold and symptom criterion determine what is counted, while the 22-hour timeframe defines the observation window. A different definition or observation period could lead to a different event count, so comparisons require consistent ascertainment.
The record is also a reminder that design information and results are separate. Randomization and a crossover model describe how a comparison was intended to be organized; they do not show the observed outcome. Without an effect estimate and its uncertainty, a reader cannot judge the size or precision of a difference. Here, the registry lists no analyses and supplies no numerical primary-endpoint comparison.
General: statistical interpretation is strongest when the design, endpoint definition, analysis plan, missing-data approach, and results can be considered together. The registry record leaves several of these elements undocumented, including treatment sequence, handling of period effects, and the analysis population. That makes transparent reporting especially important for a small crossover study, where details of individual periods and repeated measurements can affect interpretation.
The statistical importance of the record is therefore not a demonstrated treatment effect. It is the example of a clearly stated endpoint and crossover question for which the public record does not include the analysis needed to evaluate the comparison. Recognizing that boundary prevents readers from mistaking a protocol objective or planning calculation for an observed finding.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record has substantial reporting limitations for interpreting the treatment comparison. Although the study is marked completed, no outcome analysis is listed. The primary endpoint has no reported treatment-specific values, estimated contrast, confidence interval, or test result. Secondary-outcome results are also not reported. As a result, neither the direction nor the precision of the findings can be evaluated.
The recorded enrollment is 11, and the study population is adolescents with type 1 diabetes. This describes the scope of the recorded study but does not establish how many participants completed both treatment conditions or contributed primary-endpoint data. The protocol summary's expected retention of 10/12 is a planning expectation, not an observed analysis count. Generalizability beyond the population studied cannot be established from the record.
The crossover design has features that require detail for appraisal. Treatment sequence, period duration, washout procedures, and handling of possible period or carryover effects are not reported in the registry record. The study was unmasked, and the endpoint includes moderate hypoglycemic symptoms; the record does not explain how symptoms were assessed or whether assessment procedures reduced the potential influence of knowledge of treatment.
The endpoint is reported over a 22-hour timeframe. The protocol summary describes inpatient challenges involving 30 minutes of mild exercise and 3 meals, but the available description does not fully specify the insulin-coverage procedures. The record also does not report the statistical model, missing-data approach, analysis populations, or multiplicity strategy.
These limitations concern what can be learned from the registry record; they do not demonstrate that the study procedures or analyses were inadequate. They mean that the posted information is insufficient to assess the comparative efficacy, precision, robustness, or treatment-specific safety findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Hypoglycemia Prevention After Exercise in Adolescent T1DM Patients Using a Control to Range System — NCT01390259.
- Registry record last updated 2014-08-15; status last verified 2014-07.
- Results first posted 2014-08-15.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes NCT01390259, titled Hypoglycemia Prevention After Exercise in Adolescent T1DM Patients Using a Control to Range System. It lists type 1 diabetes mellitus as the condition, University of Virginia as the sponsor, and the study as completed. The recorded start date is 2010-01, the primary completion date is 2011-02, and enrollment is 11.
The design is randomized, unmasked, and crossover. It compares open-loop insulin management, in which participants were in charge of treatment, with closed-loop control, in which a computer made recommendations. The primary endpoint is hypoglycemic events per patient over 22 hours; the record also lists percent time in euglycemia and mean glucose as secondary outcomes.
The primary endpoint definition is reported, but no comparative outcome analysis is listed. Treatment-specific results, uncertainty estimates, missing-data methods, and the statistical analysis plan are not reported in the registry record. The record therefore documents the trial question and design but does not provide the results needed to evaluate the primary comparison.